Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003 is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions.
Alsop,
Constituents within pulp mill effluent deplete retinoid stores in white sucker and bind to rainbow trout retinoic acid receptors and retinoid X receptors.
2003, Pubmed
Alsop,
Constituents within pulp mill effluent deplete retinoid stores in white sucker and bind to rainbow trout retinoic acid receptors and retinoid X receptors.
2003,
Pubmed
Barak,
PPAR gamma is required for placental, cardiac, and adipose tissue development.
1999,
Pubmed
Blumberg,
Multiple retinoid-responsive receptors in a single cell: families of retinoid "X" receptors and retinoic acid receptors in the Xenopus egg.
1992,
Pubmed
,
Xenbase
Chamorro-García,
Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism.
2012,
Pubmed
Collins,
Teratology of retinoids.
1999,
Pubmed
Dawson,
Synthetic retinoids and their nuclear receptors.
2004,
Pubmed
Elmazar,
RARalpha-mediated teratogenicity in mice is potentiated by an RXR agonist and reduced by an RAR antagonist: dissection of retinoid receptor-induced pathways.
1997,
Pubmed
Ferré,
The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.
2004,
Pubmed
Fort,
Enhancing the predictive validity of Frog Embryo Teratogenesis Assay--Xenopus (FETAX).
2002,
Pubmed
,
Xenbase
Greene,
Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping.
1995,
Pubmed
Grimaldi,
Reporter cell lines to evaluate the selectivity of chemicals for human and zebrafish estrogen and peroxysome proliferator activated γ receptors.
2015,
Pubmed
Grün,
Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling.
2006,
Pubmed
Grün,
Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates.
2006,
Pubmed
,
Xenbase
Hashimoto,
Nuclear receptor antagonists designed based on the helix-folding inhibition hypothesis.
2005,
Pubmed
Hu,
Use of the enhanced frog embryo teratogenesis assay-Xenopus (FETAX) to determine chemically-induced phenotypic effects.
2015,
Pubmed
,
Xenbase
Hu,
An assay to determine the sensitive window of embryos to chemical exposure using Xenopus tropicalis.
2016,
Pubmed
,
Xenbase
Inoue,
Screening of agonistic activities against four nuclear receptors in wastewater treatment plants in Japan using a yeast two-hybrid assay.
2011,
Pubmed
Janesick,
Active repression by RARγ signaling is required for vertebrate axial elongation.
2014,
Pubmed
,
Xenbase
Janesick,
RIPPLY3 is a retinoic acid-inducible repressor required for setting the borders of the pre-placodal ectoderm.
2012,
Pubmed
,
Xenbase
Kanayama,
Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway.
2005,
Pubmed
Kanayasu-Toyoda,
HX531, a retinoid X receptor antagonist, inhibited the 9-cis retinoic acid-induced binding with steroid receptor coactivator-1 as detected by surface plasmon resonance.
2005,
Pubmed
Kastner,
Genetic analysis of RXR alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis.
1994,
Pubmed
Kliewer,
Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
1994,
Pubmed
Kubota,
PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.
1999,
Pubmed
Lehmann,
Retinoids selective for retinoid X receptor response pathways.
1992,
Pubmed
Li,
A two-hybrid yeast assay to quantify the effects of xenobiotics on retinoid X receptor-mediated gene expression.
2008,
Pubmed
Li,
The association between prenatal exposure to organochlorine pesticides and thyroid hormone levels in newborns in Yancheng, China.
2014,
Pubmed
Lyssimachou,
The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.
2015,
Pubmed
Mangelsdorf,
Retinoid receptors.
1993,
Pubmed
Michalik,
PPAR expression and function during vertebrate development.
2002,
Pubmed
,
Xenbase
Nahoum,
Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function.
2007,
Pubmed
Nishikawa,
Involvement of the retinoid X receptor in the development of imposex caused by organotins in gastropods.
2004,
Pubmed
Perlmann,
Two distinct dimerization interfaces differentially modulate target gene specificity of nuclear hormone receptors.
1996,
Pubmed
Riu,
Halogenated bisphenol-A analogs act as obesogens in zebrafish larvae (Danio rerio).
2014,
Pubmed
Rosen,
PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro.
1999,
Pubmed
Rosen,
PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth.
2001,
Pubmed
Sambrook,
Calcium-phosphate-mediated Transfection of Eukaryotic Cells with Plasmid DNAs.
2006,
Pubmed
Tontonoz,
Fat and beyond: the diverse biology of PPARgamma.
2008,
Pubmed
Turusov,
Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.
2002,
Pubmed
Willhite,
Receptor-selective retinoid agonists and teratogenic activity.
1996,
Pubmed
Yu,
Teratogenic effects of triphenyltin on embryos of amphibian (Xenopus tropicalis): a phenotypic comparison with the retinoid X and retinoic acid receptor ligands.
2011,
Pubmed
,
Xenbase
Yuan,
Stage-specific malformations and phenotypic changes induced in embryos of amphibian (Xenopus tropicalis) by triphenyltin.
2011,
Pubmed
,
Xenbase
Zhen,
Identification of retinoic acid receptor agonists in sewage treatment plants.
2009,
Pubmed
Zhu,
Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos.
2014,
Pubmed
,
Xenbase
